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Further investigation into the mechanism of tachykinin NK(2) receptor-triggered serotonin release from guinea-pig proximal colon.
Full Abstract
The effects of the monoamine oxidase A (MAO-A) inhibitor clorgyline, the L-type calcium-channel blocker nicardipine, the syntaxin inhibitor botulinum toxin type C, and the potent thiol-oxidant phenylarsine oxide (PAO) on the selective tachykinin NK(2)-receptor agonist [beta-Ala(8)]-neurokinin A(4-10) [betaAla-NKA-(4-10)]-evoked 5-hydroxytryptamine (5-HT) outflow from colonic enterochromaffin (EC) cells was investigated in vitro using isolated guinea-pig proximal colon. The betaAla-NKA-(4-10)-evoked outflow of 5-HT from clorgyline-treated colonic strips was markedly higher than that from clorgyline-untreated colonic strips. The betaAla-NKA-(4-10)-evoked 5-HT outflow from the clorgyline-treated colonic strips was sensitive to nicardipine or botulinum toxin type C. Moreover, PAO concentration-dependently suppressed the betaAla-NKA-(4-10)-evoked 5-HT outflow from the clorgyline-treated colonic strips. The suppressant action of PAO was reversed by the reducing agent dithiothrietol, but was not blocked by the protein tyrosine kinase inhibitor genistein. These results suggest that the tachykinin NK(2) receptor-triggered 5-HT release from guinea-pig colonic EC cells is mediated by syntaxin-related exocytosis mechanisms and that colonic mucosa MAO-A activity has the important function of modulating the tachykinin NK(2) receptor-triggered 5-HT release. It also appears that PAO-mediated sulfhydryl oxidation plays a role in modulating the tachykinin NK(2) receptor-triggered 5-HT release through a mechanism independent of inhibition of protein tyrosine phosphatase activity.
Author information
Author/s: Kojima, Shu-Ichi (S); Ikeda, Masashi (M); Kamikawa, Yuichiro (Y);
Affiliation: Department of Pharmacology, Dokkyo Medical University School of Medicine, Japan. s-kojima(-atsign-)dokkyomed.ac.jp
Journal and publication information
Publication Type: In Vitro; Journal Article
Journal: Journal of pharmacological sciences (J Pharmacol Sci), published in Japan. (Language: eng)
Reference: 2009-May; vol 110 (issue 1) : pp 122-6
Dates: Created 2009/05/15; Completed 2009/07/02;
PMID: 19423952, status: MEDLINE (last retrieval date: 7/2/2009, IMS Date: )
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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